{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:44:12Z","timestamp":1785512652302,"version":"3.56.0"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:00:00Z","timestamp":1573776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472924"],"award-info":[{"award-number":["81472924"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81620108026"],"award-info":[{"award-number":["81620108026"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Thyroid hormone triiodothyronine (T3) plays an important role in coordinated endochondral ossification and hypertrophic differentiation of the growth plate, while aberrant thyroid hormone function appears to be related to skeletal malformations, osteoarthritis, and Kashin-Beck disease. The T-2 toxin, present extensively in cereal grains, and one of its main metabolites, HT-2 toxin, are hypothesized to be potential factors associated with hypertrophic chondrocyte-related osteochondropathy, known as the Kashin-Beck disease. In this study, we investigated the effects of T3 and HT-2 toxin on human chondrocytes. The immortalized human chondrocyte cell line, C-28\/I2, was cultured in four different groups: controls, and cultures with T3, T3 plus HT-2 and HT-2 alone. Cytotoxicity was assessed using an MTT assay after 24-h-exposure. Quantitative RT-PCR was used to detect gene expression levels of collagen types II and X, aggrecan and runx2, and the differences in runx2 were confirmed with immunoblot analysis. T3 was only slightly cytotoxic, in contrast to the significant, dose-dependent cytotoxicity of HT-2 alone at concentrations \u2265 50 nM. T3, together with HT-2, significantly rescued the cytotoxic effect of HT-2. HT-2 induced significant increases in aggrecan and runx2 gene expression, while the hypertrophic differentiation marker, type X collagen, remained unchanged. Thus, T3 protected against HT-2 induced cytotoxicity, and HT-2 was an inducer of the pre-hypertrophic state of the chondrocytes.<\/jats:p>","DOI":"10.3390\/toxins11110667","type":"journal-article","created":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T11:25:56Z","timestamp":1573817156000},"page":"667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cytotoxic Properties of HT-2 Toxin in Human Chondrocytes: Could T3 Inhibit Toxicity of HT-2?"],"prefix":"10.3390","volume":"11","author":[{"given":"Feng\u2019e","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Public Health, Health Science Center of Xi\u2019an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People\u2019s Republic of China, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6181-9904","authenticated-orcid":false,"given":"Mikko Juhani","family":"Lammi","sequence":"additional","affiliation":[{"name":"School of Public Health, Health Science Center of Xi\u2019an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People\u2019s Republic of China, Xi\u2019an 710061, China"},{"name":"Department of Integrative Medical Biology, University of Ume\u00e5, 90187 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanzhen","family":"Shao","sequence":"additional","affiliation":[{"name":"School of Public Health, Health Science Center of Xi\u2019an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People\u2019s Republic of China, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Health Science Center of Xi\u2019an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People\u2019s Republic of China, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Health Science Center of Xi\u2019an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People\u2019s Republic of China, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Public Health, Health Science Center of Xi\u2019an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People\u2019s Republic of China, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Public Health, Health Science Center of Xi\u2019an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People\u2019s Republic of China, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.1210\/endo.141.10.7733","article-title":"Thyroid hormone acts directly on growth plate chondrocytes to promote hypertrophic differentiation and inhibit clonal expansion and cell proliferation","volume":"141","author":"Robson","year":"2000","journal-title":"Endocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/S1043-2760(03)00144-9","article-title":"The molecular actions of thyroid hormone in bone","volume":"14","author":"Bassett","year":"2003","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13075-015-0541-5","article-title":"Thyroid hormone enhance the biomechanical functionality of scaffold-free neocartilage","volume":"17","author":"Lee","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1002\/jcb.25515","article-title":"3,3\u2032,5-triiodo-L-thyronine increases in vitro chondrogenesis of mesenchymal stem cells from umbilical cord stroma through SRC2","volume":"117","author":"Mateos","year":"2016","journal-title":"J. Cell. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1359\/jbmr.070806","article-title":"Thyroid hormone interacts with the Wnt\/\u03b2-catenin signaling pathway in the terminal differentiation of growth plate chondrocytes","volume":"22","author":"Wang","year":"2007","journal-title":"J. Bone Miner. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"94","DOI":"10.2106\/00004623-195436010-00013","article-title":"Growth and differentiation of the skeleton in thyreoidectomized-hypophysectomized rats treated with thyroxin, growth hormone, and combination","volume":"36","author":"Ray","year":"1954","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.joca.2012.12.013","article-title":"Deiodinase 2 upregulation demonstrated in osteoarthritis patients cartilage causes cartilage destruction in tissue-specific transgenic rats","volume":"21","author":"Nagase","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"A43","DOI":"10.1016\/j.jval.2014.03.258","article-title":"PMS13-Study on mechanism of type 2 deiodinase gene and Erk signal transduction in Kashin-Beck disease","volume":"17","author":"Xiong","year":"2014","journal-title":"Value Health"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wen, Y., Zhang, F., Li, C., He, S., Tan, W., Lei, Y., Zhang, Q., Yu, H., Zheng, J., and Guo, X. (2014). Gene expression analysis suggests bone development-related genes GDF5 and DIO2 are involved in the development of Kashin-Beck disease in children rather than adults. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103618"},{"key":"ref_10","first-page":"1","article-title":"Occurrence data of trichothecene mycotoxins T-2 toxin and HT-2 toxin in food and feed","volume":"7","year":"2010","journal-title":"EFSA Support. Publ."},{"key":"ref_11","first-page":"851","article-title":"Comparison of T-2 toxin and HT-2 toxin distributed in the skeletal system with that in other tissues of rats by acute toxicity test","volume":"30","author":"Yu","year":"2017","journal-title":"Biomed. Environ. Sci"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jtemb.2017.08.009","article-title":"Selenium promotes metabolic conversion of T-2 toxin to HT-2 toxin in cultured human chondrocytes","volume":"44","author":"Yu","year":"2017","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1021\/jf200767q","article-title":"T-2 toxin, a trichothecene mycotoxin: Review of toxicity, metabolism, and analytical methods","volume":"59","author":"Li","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yu, F.F., Lin, X.L., Wang, X., Ping, Z.G., and Guo, X. (2019). Comparison of apoptosis and autophagy in human chondrocytes induced by the T-2 and HT-2 toxins. Toxins, 11.","DOI":"10.3390\/toxins11050260"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Liu, J., Wang, L., Guo, X., Pang, Q., Wu, S., Wu, C., Xu, P., and Bai, Y. (2014). The role of mitochondria in T-2 toxin-induced human chondrocytes apoptosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108394"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.molimm.2017.08.019","article-title":"Inflammatory cytokine of IL-1\u03b2 is involved in T-2 toxin-triggered chondrocyte injury and metabolism imbalance by the activation of Wnt\/\u03b2-catenin signaling","volume":"91","author":"Chang","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1039\/C5TX00377F","article-title":"The effects of T-2 toxin on the prevalence and development of Kashin-Beck disease in China: A meta-analysis and systematic review","volume":"5","author":"Li","year":"2016","journal-title":"Toxicol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"269","DOI":"10.22203\/eCM.v028a19","article-title":"Role and regulation of RUNX2 in osteogenesis","volume":"28","author":"Bruderer","year":"2014","journal-title":"Eur. Cell Mater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1210\/en.2014-1109","article-title":"Chondrocytes play a major role in the stimulation of bone growth by thyroid hormone","volume":"155","author":"Desjardin","year":"2014","journal-title":"Endocrinology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.joca.2014.07.023","article-title":"Recent advances in the research of an endemic osteochondropathy in China: Kashin-Beck disease","volume":"22","author":"Guo","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/2049-1891-3-39","article-title":"Fibroblast growth factor receptor 3 effects on proliferation and telomerase activity in sheep growth plate chondrocytes","volume":"3","author":"Smith","year":"2012","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1089\/ten.tea.2013.0023","article-title":"Thyroid hormone-induced hypertrophy in mesenchymal stem cell chondrogenesis is mediated by bone morphogenetic protein-4","volume":"20","author":"Karl","year":"2014","journal-title":"Tissue Eng. A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1002\/art.1780350715","article-title":"Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy","volume":"35","author":"Kirsch","year":"1992","journal-title":"Arthritis Rheumatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1089\/ten.tea.2016.0533","article-title":"Thyroxine increases collagen type II expression and accumulation in scaffold-free tissue-engineered articular cartilage","volume":"24","author":"Whitney","year":"2018","journal-title":"Tissue Eng. A"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.etp.2017.05.010","article-title":"A study on role of triiodothyronine (T3) hormone on the improvement of articular cartilage surface architecture","volume":"69","author":"Jia","year":"2017","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.tiv.2010.12.001","article-title":"Effects of T-2 toxin and selenium on chondrocyte expression of matrix metalloproteinases (MMP-1, MMP-13), \u03b12-macroglobulin (\u03b12M) and TIMPs","volume":"25","author":"Chen","year":"2011","journal-title":"Toxicol. Vitro"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, Y., Zou, N., Wang, J., Wang, K.W., Li, F.Y., Chen, F.X., Sun, B.Y., and Sun, D.J. (2017). TGF-\u03b21\/Smad3 signaling pathway mediates T-2 toxin-induced decrease of type II collagen in cultured rat chondrocytes. Toxins, 9.","DOI":"10.3390\/toxins9110359"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1631\/jzus.B071322","article-title":"Promotion of the articular cartilage proteoglycan degradation by T-2 toxin and selenium protective effect","volume":"9","author":"Li","year":"2008","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.tiv.2012.07.002","article-title":"T-2 toxin enhances catabolic activity of hypertrophic chondrocytes through ROS-NF-\u03baB-HIF-2\u03b1 pathway","volume":"26","author":"Tian","year":"2012","journal-title":"Toxicol. Vitro"},{"key":"ref_30","first-page":"23","article-title":"Immortalization of human articular chondrocytes for generation of stable, differentiated cell lines","volume":"100","author":"Goldring","year":"2004","journal-title":"Methods Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/11\/667\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:34:38Z","timestamp":1760189678000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/11\/667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,15]]},"references-count":31,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["toxins11110667"],"URL":"https:\/\/doi.org\/10.3390\/toxins11110667","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,15]]}}}